Cell and Tissue Banking

, Volume 7, Issue 4, pp 265–305 | Cite as

Transfusion and transplantation of cryopreserved cells and tissues

  • Sajio Sumida
Advances in Tissue Banking


The modern era of cryomedicine began in 1949 in London and developed world-wide in the second half of the 20th century based on the first report of a novel method of cryopreservation of sperm and erythrocytes using glycerol that was reported in 1949 and 1950 by Polge and Smith. In 1951 at Hradec Kralove, Czech. Klen initiated a “tissue bank” using his unique freeze-drying system. In 1964, the initial meeting of the Society for Cryobiology was organized by its first president. B. J. Luyet in Washington, DC. Cryobiology including cryopreservation and cryosurgery, contributed immense advances for clinical medicine. Cryomedicine will realize the goals of the New Millennium medicine: regeneration, plasticity, and minimally invasive therapy. I explained the first one, regeneration in this paper in detail.

Cryomedicine involved subzero-temperatures to freeze the biological objects either for preservation or for destruction. Cryopreservation involves the cooling of the target biological materials to below the temperature of solidification by consumption of energy, through continuously supplying inert cryogens to attain the necessary cryo-temperatures by Joule-Thompson’s effect. Therefore biological materials for cryopreservation should be carefully selected and once frozen purposefully kept in the frozen state to be used later to regenerate human cells, tissues and organs, and also to relaize “plasticity”. Recently, lyophilization of human cells and tissues came back to the main street of cryopreservation to provide low cost economical and ecological banking of cells and tissues as a hope of the New Millennium. The first attempt of that was made by Prof. Dr. Rudolf Klen and his colleagues.

Finally, physicians and related scientists who are going to be interested in cryomedicine should not worry about “freezing and thawing” as being time consuming and labor intensive, otherwise they will not share in the crucial benefits of cryomedicine.


Cryopreservation Transfusion Tissue banking 


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I am deeply indebted to my old friend, Dr. A.W. Rowe, who proofread and corrected the manuscript of this review on the basis of his profound knowledges of Cryobiology and Medicine. Without his support, this review would not be completed. The researches introduced in this review were supported by Grants from the Ministry of Health and Labor, the National Institute of Health (Japan), and Foundation of␣New Technology Development (Japan) from 1970 to␣1999.


  1. Alving BM, Reid TJ, Fratantoni JC et al (1997) Frozen platelets and platelet substitutes in transfusion medicine. Transfusion 37:866–876PubMedCrossRefGoogle Scholar
  2. Appelbaum FR, Herzig GP, Ziegler RG et al (1978) Successful engraftment of cryopreserved autologous bone marrow in patients with malignant lymphoma. Blood 52:85PubMedGoogle Scholar
  3. Asahina E (1966) Freezing and frost resistance in insects. In: Meryman HT (eds) Cryobiology. Academic Press, New York, pp 451–484Google Scholar
  4. Asahina E, Aoki K, Shinozaki J (1954) The freezing process of frost-hardy caterpillars. Bull Ent Res 45:329–339CrossRefGoogle Scholar
  5. Bessis M (1973). Red cell shapes, an illustrated classification and its rationale. In: Bessis M, Weed RI, Leblond PF (eds) Red cell shape, physiology, pathology, ultrastructure. Springer Verlag, New York, pp 1–25Google Scholar
  6. Bode AP (1995) Preclinical testing of lyophilized platelets as a product for transfusion medicine. Transfus Sci 16:183–185PubMedCrossRefGoogle Scholar
  7. Bode AP, Read MS, Reddlick RL (1999) Activation and adherence of lyophilized human platelets on canine vessel strips in the Baumgartner perfusion chamber. J Lab Clin Med 133:200–201PubMedCrossRefGoogle Scholar
  8. Buckner CD (1983) Critical issues in autologous marrow transplantation. J Cell Biochem 7A:52Google Scholar
  9. Curry S (1982) Methemoglobinemia. Ann Emerg Med 11: 214–22Google Scholar
  10. Dayian G, Rowe AW (1976) Cryopreservation of human platelets for transfusion. A glycerol-glucose, moderate rate cooling procedure. Cryobiology 13:1–8PubMedCrossRefGoogle Scholar
  11. Ebine K (2002) Clinical application of cryopreserved autologous red blood cells and platelets in cardiovascular surgery (in Japanese). J Clin Exp Med (IGKU NO AYUMI) 201(11):819–825Google Scholar
  12. Eichler H, Beck C, Bernard F et al (2002) Use of recombinant human deoxyribonuclease (DNase) for processing of a thawed umbilical cord blood transplant in a patient with relapsed acute lymphoblastic leukemia. Ann Hematol 81(3):170–173PubMedCrossRefGoogle Scholar
  13. Fadok VA, Voelker DR, Campbell PA et al (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 148(7):2207–2216PubMedGoogle Scholar
  14. Fadok VA, Bratton DL, Frasch SC et al (1998) The role of phosphatidylserine in recognition of apoptotic cells by phagocytes. Cell Death Differ 5:551–562PubMedCrossRefGoogle Scholar
  15. Fadok VA, Bratton DL, Rose DM et al (2000) A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405:85–90PubMedCrossRefGoogle Scholar
  16. Fadok VA, de Cathelineau A, Daleke DL, Henson PM, Bratton DL (2001) Loss of phospholipids asymmetry and surface exposure of phosphatidylserine is required for phagocytosis of apoptotic cells by macrophages and fibroblasts. J Biol Chem 276:1071–1077PubMedCrossRefGoogle Scholar
  17. Fawcett K, Barr AR (1987) Tissue banking. American Association of Blood Banks, Arlington VirginiaGoogle Scholar
  18. Franks F, Mathias S (1982) Biophysics of water. John Wiley, ChichesterGoogle Scholar
  19. Gaffney BJ (1976) Practical considerations for the calculation of order parameters for fatty acid or phospholipids spin labels in membranes. In: Berliner LJ (ed) Spin labeling – theory and applications, Appendix IV. Academic Press, New YorkGoogle Scholar
  20. Gale RP (1980) Autologous bone marrow transplantation in patients with cancer. JAMA 243:540–542PubMedCrossRefGoogle Scholar
  21. Gastric cancer and a simple laparotomy: Program of the 34th meeting of gastric cancer research society (Igan Kenkyukai) at Hiroshima, on January 19, 1980Google Scholar
  22. Glassman AB, Umlas J (eds) (1983) Cryopreservation of tissue and solid organs for transplantation. American Association of Blood Banks, Arlington, VirginiaGoogle Scholar
  23. Gonzales F, Luyet B (1950) Resumption of heart-beat in chick embryo frozen in liquid nitrogen. Biodynamica 7:1–5PubMedGoogle Scholar
  24. Green RM (2001) Four moral questions for human embryonic stem cell research. Wound Repair Regen 9(6):425–428PubMedCrossRefGoogle Scholar
  25. Griffith AA (1920) The phenomena of rupture and flaw in solids. Philos Trans R Soc London Ser A 221:163–198Google Scholar
  26. Harada M, Ishino C, Okaka K et al (1982) Conditions for cryopreservation of human bone marrow for use in autologous transplantation. Acta Hematol Jpn 45(4):754–792Google Scholar
  27. Hartert H (1948) Blutgerinnungenstudien mit der Thrombelastographie einem neuen Unterrsuchungsverfahren. Klin Wochenschr 26:577–583CrossRefPubMedGoogle Scholar
  28. Hocking D, Olsen RE (1980) Platelet cryopreservation. A simple routine. Med J Aust 1:537–538PubMedGoogle Scholar
  29. Huggins C (1963) Preservation of blood for transfusions by freezing with dimethylsulfoxide and a novel washing technique. Surgery 54(1):191–194PubMedGoogle Scholar
  30. Huggins C (1965) Frozen blood. J Jpn Soc Blood Transfus 12:67–68Google Scholar
  31. Huggins CE, Russell PS, Winn HJ et al (1973) Frozen blood in transplant patients: hepatitis and HL-A isosensitization. Transplant Proc 5(1):809–812PubMedGoogle Scholar
  32. Kasai M, Zhu SE, Pedro PB et al (1996) Fracture damage of embryos and its prevention during vitrification and warming. Cryobiology 33:459–464PubMedCrossRefGoogle Scholar
  33. Keller G (1995) In vitro differentiation of embryonic stem cells. Curr Opin Cell Biol 7:862–869PubMedCrossRefGoogle Scholar
  34. Khuri SF, Healey N, Macgregor H et al (1999) Comparison of the effects of transfusions of cryopreserved and liquid-preserved platelets on haemostasis and blood loss after cardiopulmonary bypass. J Thoracic Cardiovasc Surg 117:172–183CrossRefGoogle Scholar
  35. Klen R (1982) Biological principles of tissue banking. England, Pergamon Press, OxfordGoogle Scholar
  36. Körbling M, Katz R, Khanna A et al (2002) Hepatocytes and epithelial cells or donor origin in recipients of peripheral blood stem cells. N Engl J Med 346(10):738–746PubMedCrossRefGoogle Scholar
  37. Kusaba A, Moriyama M, Kiyose T et al (1975) An experimental studies on freeze-dried homologous vein grafts for peripheral arterial reconstruction. Low Temp Med 1(1):74–80Google Scholar
  38. Lacy P, Kostianovsky M (1967) Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16:35–39PubMedGoogle Scholar
  39. Lovelock JE (1952) Re-suspension in plasma of human red blood cells frozen in glycerol. Lancet 1:1238PubMedCrossRefGoogle Scholar
  40. Lovelock JE (1953) The mechanism of the protective action of glycerol against hemolysis by freezing and thawing. Biochim Biopys Acta 11:28–36CrossRefGoogle Scholar
  41. Lovelock JE (1954) The protective action of neutral solutes against haemolysis by freezing and thawing. Biochem J 56:265–270PubMedGoogle Scholar
  42. Lovelock JE (1957) Denaturation of lipid-protein complexes as a cause of damage by freezing. Proc Rec Soc (London) 147B:426Google Scholar
  43. Luyet B (1960) On various phase transitions occurring in aqueous solutions at low temperatures. Ann N Y Acad Sci 85:549–569PubMedGoogle Scholar
  44. Luyet B (1966) On the possible biological significance of some physical changes encountered in the cooling and the rewarming of aqueous solutions. In: Asahina E (ed) Cellular injury and resistance in freezing organisms. Proceedings of the international conference on low temperature science, the institute of low temperature science, Hokkaido University, Japan 1966, pp 1–20Google Scholar
  45. Luyet B, Hodapp EL (1938) Revival of frog’s spermatozoa vitrified in liquid air. Proc Soc Exp Biol Med 39:433–435Google Scholar
  46. Luyet B, Rapatz G (1970) A review of basic researchers on the cryopreservation of red blood cells. Crybiology 6(5):425–482Google Scholar
  47. Luyet B, Rapatz GL, Gehenio P (1963) On the mode of action of rapid cooling in the preservation of erythrocytes in frozen blood. Biodynamica 9:95–124PubMedGoogle Scholar
  48. Metcalf D (1977) Hemopoietic Colonies. Springer-Verlag, New YorkGoogle Scholar
  49. Metcalf D (1984) Clonal culture of hemopoietic cells, technicques and applications, Elsevier, AmsterdamGoogle Scholar
  50. Metcalf D (1988) The molecular control of blood cells. Harvard Univ PressGoogle Scholar
  51. Nash T (1962) The chemical constitution of compounds which protect erythrocytes against freezing damage. J Gen Physiol 46(1):167–175PubMedCrossRefGoogle Scholar
  52. Nash T (1966) Chemical constitution and physical properties of compounds able to protect living cells against damage due to freezing and thawing. In: Meryman HT (ed) Cryobiology. Academic Press, London and New York, pp 179–211Google Scholar
  53. Ng KFJ, Lam CCK, Chan LC (2002) In vivo effect of haemodilution with saline on coagulation: a randomized controlled trial. Br J Anaesth 88(4):475–480PubMedCrossRefGoogle Scholar
  54. O’Toole T (1980) Blood cells of mammoth found frozen. Washington Post Washington DC, May 6Google Scholar
  55. Padilla-Cruz A, Sumida S (eds) (1983) Proceedings of 5th world congress of cryosurgery. University Press, Univ. of Philippines System, Diliman, Quezon CityGoogle Scholar
  56. Pauling L (1948) The nature of the chemical bond. Cornell Univ press, New YorkGoogle Scholar
  57. Polge C, Smith AU, Parks AS (1949) Revival of spermatozoa after vitrification and dehydration at low temperatures. Nature 164:666PubMedGoogle Scholar
  58. Porcu E, Flalmigni C (1997) Human oocytes from physiology to IVF. Monduzzi Editore, BolognaGoogle Scholar
  59. Pretlow II TP. Pretlow TP (eds) (1982) Cell separation, Methods and selected applications. vol 1 Academic Press, New York, LondonGoogle Scholar
  60. Puhlev I, Guo N, Brown DR et al (2001) Desiccation tolerance in human cells. Cryobiology 42:207–217PubMedCrossRefGoogle Scholar
  61. Read MS, Reddick RL, Bode AP et al (1995) Preservation of haemostatic and structural properties of rehydrated lyophilized platelets: potential for ling-term storage of dried platelets for transfusion. Proc Natl Acad Sci USA 92:397–401PubMedCrossRefGoogle Scholar
  62. Rowe AW (1967) Significance of the aqueous-ice phase transformation during controlled rate cooling of biological specimens. In: Asahina E (ed) Cellular injury and resistance in freezing organisms. Inst. Low Temp Sci. Hokkaido Univ, Japan, pp 21–23Google Scholar
  63. Rowe AW (1973) Preservation of blood by the low glycerol-rapid freeze process in “red cell freezing”. Amer. Assoc. Blood Banks 55–72Google Scholar
  64. Rowe AW, Rinfret A (1962) Controlled rate freezing of bone marrow. Blood 20:636Google Scholar
  65. Rowe AW, Eyster E, Kellner A (1968) Liquid nitrogen preservation of red blood cells for transfusion. Cryobiology 5:119–128PubMedCrossRefGoogle Scholar
  66. Rowe AW, Dayian G, Reich LM et al (1974) Cryopreservation of platelets for transfusion using a glycerol-glucose medium. In: Högman CF, Krijnen HW, Valeri CR (eds) Platelet preservation and transfusion. International Society of Blood Transfusion, Paris, p 51Google Scholar
  67. Sherman JK (1954) Freezing and freeze-drying of human spermatozoa. Fertil Steril 5:357PubMedGoogle Scholar
  68. Sherman JK (1973) Synopsis of the use of frozen human semen since 1964: state of the art of human semen banking. Fertil Steril 24:397PubMedGoogle Scholar
  69. Shinohara N, Sumida S, Masuda S (1990) Bone allografts after segmental resection of tumors. Int Orthop 14:273–276PubMedCrossRefGoogle Scholar
  70. Smith AU (1950) Prevention of hemolysis using freezing and thawing of red blood cells. Lancet 2(27): 910–912PubMedCrossRefGoogle Scholar
  71. Smith AU (1961) Biological effects of freezing and supercooling. Edward Arnold Ltd., LondonGoogle Scholar
  72. Strom SC (1982) Isolation, transplantation and culture of human hepatocytes. J Natl Cancer Inst 68:771–778PubMedGoogle Scholar
  73. Strom SC (1997) Hepatocyte transplantation as a bridge to orthotopic liver transplant in terminal liver failure. Transplantation 63:559–569PubMedCrossRefGoogle Scholar
  74. Strom TB (2001) Allogeneic stem cells, clinical transplantation, and the origins of regenerative medicine. Transplant Proc 33:3044–3049PubMedCrossRefGoogle Scholar
  75. Sumida S (1970) Frozen blood: Sumida’s blood freezing unit, 16 mm movie. Dentsu Co. Ltd., JapanGoogle Scholar
  76. Sumida S (1973: 1st edn., 1974: 2nd edn.) Transfusion of blood preserved by freezing. Lippincott-Geroge Thieme Publ. StuttgartGoogle Scholar
  77. Sumida S (1976) In vivo survival of 51Cr labeled platelets preserved at the room temperature or at the frozen state with or without prostaglandin E1. Low Temp Med 2:131–135Google Scholar
  78. Sumida S (1980) Frozen blood, 16 mm movie/video in English. Dentsu Movie Co., Tokyo, JapanGoogle Scholar
  79. Sumida S (1982) Cryomedicine, 16 mm movie. Dentsu Movie Co., Tokyo, JapanGoogle Scholar
  80. Sumida S (1988) Cryomedicine. In: Advances in cryogenics. proceedings of the international conference on cryogenics, Calcutta, December 6–11, pp 565–613Google Scholar
  81. Sumida S (1993a) Cryopreservation of human blood cells. In: Recent advances in cryomedicine and cryobiology. Proceedings of 2nd Asia-Pacific congress of low temperature medicine, 5th China-Japan congress of low temperature medicine, October 11–14, 1993, Xian, China, International Academic Publ. Beijing, pp 3–15Google Scholar
  82. Sumida S (1993b) Cryopreservation of human blood cells. In: Agishi E et al (eds) Therapeutic plasmapheresis (XII). VSP, pp 3–11Google Scholar
  83. Sumida S (2000) Transfusion medicine in the new millennium. Kanehara Shuppan Book Publ., Tokyo (in Japanese. Figures and tables in English)Google Scholar
  84. Sumida S (2005a) Mechanism of cryoablation of the tissues. In: Harada J, Miyasaka K, Sumida S (eds) Percutaneous cryotherapy of renal cell carcinoma under an open MRI system. Horizons in cancer research, vol 3. Nova Biomed. Books, NY, pp 31–48Google Scholar
  85. Sumida S (2005b) Frozen blood: reduced HLA allosensitization. Low Temp Med 31(1):1–3CrossRefGoogle Scholar
  86. Sumida S (2005c) Mechanism of cryoablation of tissues. In: Harada J, Miyasaka K, Sumida S (eds) Percutaneous cryotherapy of renal cell carcinoma under an open MRI system. Horizons in cancer research, vol 3. Nova Science Book Publishers Inc., NY, pp 31–48Google Scholar
  87. Sumida A, Aso K (eds) (1983) Low temperature medicine (TEIONIGAKU). Asakura-Shoten Book Publ (In Japanese)Google Scholar
  88. Sumida S, Oshikawa K (1996) How long can we cryopreserve stem cell of cancer patients?. Cryobiology 33:651Google Scholar
  89. Sumida S, Kitamura T (2004) How long can we cryopreserved human blood cells and stem cells as genetic resources? International conference: conservation of genetic resources (Abstract), Sponsored by IIR, St. Petersburg, Oct. 19–22Google Scholar
  90. Sumida S, Okuyama Y, Kamegai T (1967) Serum hepatitis from frozen blood. Lancet 2:1255–1256PubMedCrossRefGoogle Scholar
  91. Sumida S, Sumida M, Miyata K et al (1975) Frozen blood: HLA sensitization. Low Temp Med 1(4):227–231Google Scholar
  92. Sumida S, Eto S, Morishige F et al (1984a) High-dose chemotherapy with frozen autologous marrow transplantation in patients with poor-prognosis tumors. Jpn J Clin Oncol 14(Suppl. 1):553–562Google Scholar
  93. Sumida S, Eto S, Yamaguchi A, Kawata H (1984b) Fibrillation and contraction tracings from adult rat hearts after freezing in liquid nitrogen for ten years. Low Temp Med 10(3):47–51Google Scholar
  94. Sumida S, Eto S, Watanabe E (1984c) Frozen blood for cancer patients. Low Temp Med 10(3):43–46Google Scholar
  95. Sumida S, Ebine K, Tamura S et al (1987) Viability of supercooled donor hearts for transplantation. Cryobiology 24:570–671CrossRefGoogle Scholar
  96. Sumida S, Xi Y, Oshikawa K (1997) How long can we cryopreserve stem cell of cancer patients? 80% of progenitors viable for 38 years in liquid nitrogen. Cryobiology 35:334Google Scholar
  97. Tablin F, Walkers N, Walkers WF, Oliver AE, Tsvetkova NM, Crowe JH (2001) Successful freeze drying of human platelets with trehalose. Abstract. Cryobiology 43(4):317–318Google Scholar
  98. Tammann G (1898) Z Phys Chem 25:441, 25:472 (Luyet 1940)Google Scholar
  99. Thompson RB (1975) The use of frozen platelet concentrates (abstract). The 10th congress of international society of blood transfusion. HelsinkiGoogle Scholar
  100. Thomson JA, Itskovitz-Eldor J, Shapiro SS et al (1998) Embryonic stem cell lines derived from human blastocyts. Science 282:1145–1147PubMedCrossRefGoogle Scholar
  101. Tobias JS, Tatersall MHN (1976) Perspective in cancer research. Autologous marrow support and intensive chemotherapy in cancer patients. Eur J Cancer 12:1PubMedGoogle Scholar
  102. Traverso CI, Caprini JA (1993) Monitoring systemic anticoagulation in cardiovascular surgery. In: Pifarré R (ed) Anticoagulation, hemostasis, and blood preservation in cardiovascular surgery. Hnley & Belfus INC., PhiladelphiaGoogle Scholar
  103. Triffitt JT (2002) Stem cells and the philosopher’s stone. J Cell Biochem Suppl(38):13–19CrossRefGoogle Scholar
  104. Vadhan-Raj S, Kavanagh JJ, Freedman RS et al (2002) Safety and efficacy of transfusions of autologous cryopreserved platelets derived from recombinant human thrombopoietin to support chemotherapy-associated severe thrombocytopenia: a randomized cross-over study. Lancet 359:2145–2152PubMedCrossRefGoogle Scholar
  105. Valeri CR, Ragno G, Pivacek LE et al (2000) An experiment with glycerol-frozen red blood cells stored at −80°C for up to 37 years. Vox Sang 79: 168–174PubMedCrossRefGoogle Scholar
  106. Vaughn C, Mychaskiw G, Sewell P (2002) Massive hemorrhage during radiofrequency ablation of a pulmonary neoplasm. Anesth Analg 94(5):1149–1151PubMedCrossRefGoogle Scholar
  107. Walker LK, Casella JF, Nichols DG (1995) Polycythemia, methemoglobinemia, and porphyria: perioperative management and evaluation. In: Lake CL, Moore RA (eds), Blood, hemostasis, transplantation, and alternatives in the perioperative period. Raven Press, New York, pp 447–453Google Scholar
  108. Yagi H, Sato M, Ueda H, Sumida S (1976) A simple technique of the skin preservation using the icebox of a home refrigerator. Low Temp Med 2(3):137–141Google Scholar
  109. Yagi H, Ueda H, Sumida S (1978) A simple technique of the skin preservation using the icebox of a home refrigerator (abstract). Cryobiology 15:723CrossRefGoogle Scholar
  110. Yamaguchi A (1973) Studies on the freeze-preservation of heart (in Japanese with English summary). Toho Univ Med J 20(3,4):314–329Google Scholar
  111. Zhelezny BV (1978) The density of supercooled water. Zhurnal Fizicheskoi Khimii 43(9):2343–2344Google Scholar
  112. Zwaal RJA, Schroit AJ (1997) Pathophysiologic implications of membrane phospholipids asymmetry in blood cells. Blood 89:1121–1123PubMedGoogle Scholar

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© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  1. 1.Sumida Laboratory of Cryomedicine and Blood TransfusionTokyoJapan
  2. 2.Wakkanai Teishinkai HospitalWakkanaiJapan

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